Completely Changing Current Ways of Thinking – New Breakthrough Could Lead to Better Cancer Treatments

Cancer Cells Illustration

The place where cancer starts in the body is called the primary cancer or primary site. Cells from the primary site may break away and spread to other parts of the body. These cells can then grow and form other tumors. These are called secondary cancers or metastases.

The research improves our understanding of how cancer spreads.

Scientists funded by Cancer Research UK have found that cancer cells ‘hijack’ a process used by healthy cells to spread throughout the body, completely changing current ways of thinking about cancer metastasis.

The researchers from the Cancer Research UK Cambridge Institute at the University of Cambridge discovered that blocking the NALCN protein’s activity in mice with cancer cells triggers metastasis.

The study, which was recently published in the journal Nature Genetics, also found that this process is not just present in cancer. Unexpectedly, when NALCN was removed from mice that did not have cancer, the healthy cells in those animals began to migrate out from their original tissue and join with other organs.

Richard Gilbertson’s Group at the Cancer Research UK Cambridge Institute

A photograph of Professor Richard Gilbertson’s group at the Cancer Research UK Cambridge Institute. Credit: Cancer Research UK Cambridge Institute

They discovered, for example, that healthy pancreatic cells moved to the kidney and became healthy kidney cells. This indicates that metastasis is not an abnormal process unique to cancer, as previously thought, but rather a normal process employed by healthy cells that tumors have exploited to travel to other areas of the body and form metastases.

Group Leader for the study and Director of the Cancer Research UK Cambridge Centre, Professor Richard Gilbertson, said: “These findings are among the most important to have come out of my lab for three decades. Not only have we identified one of the elusive drivers of metastasis, but we have also turned a commonly held understanding of this on its head, showing how cancer hijacks processes in healthy cells for its own gains. If validated through further research, this could have far-reaching implications for how we prevent cancer from spreading and allow us to manipulate this process to repair damaged organs.”

Despite being one of the main causes of death in cancer patients, metastasis has remained incredibly difficult to prevent, largely because researchers have found it hard to identify key drivers of this process which could be targeted by drugs. Now that they have identified NALCN’s role in metastasis, the team is looking into various ways to restore its function, including using existing drugs on the market.

Lead researcher on the study and Senior Research Associate at the Cancer Research UK Cambridge Institute, Dr. Eric Rahrmann, said: “We are incredibly excited to have identified a single protein that regulates not only how cancer spreads through the body, independent of tumor growth, but also normal tissue cell shedding and repair. We are developing a clearer picture on the processes that govern how cancer cells spread. We can now consider whether there are likely existing drugs which could be repurposed to prevent this mechanism from triggering cancer spreading in patients.”

Cancer Research UK’s Director of Research, Dr. Catherine Elliott, said: “Once cancer has spread from the first tumor, it is harder to treat because we are looking at multiple sites in the body and working with new tumors that may be resistant to treatment. Discovering that a cancer has spread is always devastating news for patients and their families and so we are delighted to have supported this incredible research which may one day allow us to prevent metastasis and turn cancer into a much more survivable disease.”

Reference: “The NALCN channel regulates metastasis and nonmalignant cell dissemination” by Eric P. Rahrmann, David Shorthouse, Amir Jassim, Linda P. Hu, Mariaestela Ortiz, Betania Mahler-Araujo, Peter Vogel, Marta Paez-Ribes, Atefeh Fatemi, Gregory J. Hannon, Radhika Iyer, Jay A. Blundon, Filipe C. Lourenço, Jonathan Kay, Rosalynn M. Nazarian, Benjamin A. Hall, Stanislav S. Zakharenko, Douglas J. Winton, Liqin Zhu, and Richard J. Gilbertson, 29 September 2022, Nature Genetics.
DOI: 10.1038/s41588-022-01182-0

The study was funded by Cancer Research UK and Cancer Research UK Cambridge Institute. 

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